AB0367 THE PARADIGM OF DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS: SUBTYPES AND EARLY IDENTIFICATION.
Authors: M. Novella-Navarro, V. Ruiz, G. Torres Ortiz, C. A. Chacur, C. Tornero, A. Villalba, R. Sanmartí, C. Plasencia, A. Balsa
Journal: Annals of the Rheumatic Diseases (2022)

Background Difficult-to-treat rheumatoid arthritis (D2TRA) 1 is an emerging concern for rheumatologists. Multiple failures to biologic or targeted specific disease modifying antirheumatic drugs (b/tsDMARDs) may be due to multi-drug inefficacy or difficulties in the optimum management of treatments due to adverse events, comorbidities, poor adherence, among others. In a previous study 2 we identified that younger patients with erosive disease and especially the early absence of clinical response to the first b/tsDMARDs were associated to multiple drug inefficacy but it is worth knowing whether these factors are the same for those patients who receive multiple b/tsDMARDs due to causes other than inefficacy. Objectives i) To describe the characteristics of a cohort of D2TRA patients in clinical practice. ii) To analyze the differences between D2TRA due to inefficacy vs D2TRA to other causes. iii) To compare the different subtypes of D2TRA with non-D2TRA. Methods This study involved patients with D2TRA from La Paz Hospital and Clìnic Hospital between 2000 and 2021. D2TRA group included patients who had received ≥2b/tsDMARDs due to inefficacy (D2TRA-inefficacy) or due to: adverse events, poor adherence, contraindications, comorbidities, drug-intolerance etc. (D2TRA-other causes). Patients who achieved low disease activity or remission (by DAS28) with the 1st bDMARD and remained with the same drug for at least 5 years were non-D2TRA patients. For all patients, demographic, clinical characteristics and laboratory parameters were assessed at baseline visit (prior to start the 1st b/tsDMARD) and after 6 months. Descriptive analysis was performed and bivariate logistic regression models were assembled. P&lt;0.05 was considered statistically significant. Odds Ratio (OR) and Confidence Intervals (CI) were calculated. IBM SPSS 21.0 Results In total, 253 patients were included, 131 were non-D2TRA and 122 D2TRA [86 (70.5%) D2TRA-inefficacy and 36 (29.5%) D2TRA-other causes]. Comparison between both groups of D2TRA patients: no differences in gender, age at b/tsDMARD starting or age at RA diagnosis were found and neither between socioeconomic status, frequency of anxiety-depression or other comorbidities. Patients D2TRA-other causes had less extra-articular manifestations than D2TRA-inefficacy (8.3% vs 26.7%; p=0.02); lower values of DAS28 at starting 1st b/tsDMARD (4.9±1.4 vs 5.7±1.2; p=0.01), and also at 6 months of treatment (3.5±1.5 vs 4.5±1.5; p=0.02) than those with D2TRA-inefficacy. 2) Comparison between Non-D2TRA patients and D2TRA-other causes: no differences in sociodemographic characteristics were found and neither differences in baseline disease activity, only differences in DAS28 at 6 months were observed, being higher D2TRA-other causes than in non-D2TRA (3.54±1.54 vs 2.93±0.99; p=0.03). Bivariate analysis only showed that high DAS28-6m was slightly associated with D2TRA-other causes (OR=1.45 CI95% 1.11-2.16). Conclusion In this cohort, around 3 out of 10 D2TRA patients dropped out multiple b/tsDMARDs for reasons other than inefficacy In contrast to D2TRA-inefficacy, patients with D2TRA-other causes are indistinguishable from non-D2TRA patients at baseline, indicating that patients with D2TRA-other causes does not seem predictable in the early stages of treatment with b/tsDMARDs, unlike what occurs with multidrug ineficacy. References [1]Nagy G. et al. Ann Rheum Dis 2020 [2]Novella-Navarro M. et al. Arthitis Res Ther 2020. Disclosure of Interests Marta Novella-Navarro: None declared, Virginia Ruiz: None declared, Gabriela Torres Ortiz: None declared, Chafik Alejandro Chacur: None declared, Carolina Tornero: None declared, Alejandro Villalba: None declared, Raimón Sanmartí Grant/research support from: Abbvie, BMS, Gebro-Pharma, Lilly, MSD, Pfizer, Sanofi and Roche, Chamaida Plasencia Speakers bureau: Pfizer, Lilly, Sandoz, Abbvie,Biogen, Roche, Sanofi, Novartis, Grant/research support from: Pfizer, Abbvie, Alejandro Balsa Speakers bureau: Pfizer, Abbvie, Lilly, Galapagos, BMS, Sandoz, Nordic, Gebro, Roche, UCB, Consultant of: Pfizer, Abbvie, Lilly, Galapagos, BMS, Nordic, Sanofi, UCB, Grant/research support from: Pfiser, Abbvie, BMS, Nordic, Gebro, Roche, UCB